Lower oesophageal sphincter hypersensitivity to opioid receptor stimulation in patients with idiopathic achalasia.

Abstract

Impairment of non-cholinergic innervation of the lower oesophageal sphincter has been suggested in idiopathic achalasia. As opioid nerves are present in the lower oesophageal sphincter and opioid peptides affect lower oesophageal sphincter motility, the effect of an opioid agonist, morphine (100 ,uggkg iv), and an opioid blocker, naloxone (80 ,ug/kg iv), on lower oesophageal sphincter motor function was assessed in 10 healthy subjects and in 10 patients with untreated idiopathic achalasia on separate days and in randomised order. In addition, in six ofthe patients, naloxone 0x8 mg iv was injected 60 minutes after morphine and recordings continued for a further five minutes. Lower oesophageal sphincter pressure was monitored by a sleeve device. In the healthy subjects morphine decreased (p<0-01) resting lower oesophageal sphincter pressure by 4 (1) mm Hg (23 (8)%). In the achalasia patients the effect was more marked, lower oesophageal sphincter pressure being reduced (p<001) by 11 (2) mm Hg (46 (8)%). Naloxone reversed lower oesophageal sphincter pressure to basal. Both absolute and percentage decreases after morphine were significantly greater (p<005) in the achalasia patients than in the healthy subjects. Swallow induced lower oesophageal sphincter relaxation was significantly decreased (p<005) by morphine in the healthy subjects but not in the achalasia patients. Naloxone had no effect on resting lower oesophageal sphincter pressure or swallow induced relaxation in either healthy subjects or achalasia patients. In conclusion achalasia patients are hypersensitive to the effect of morphine on resting lower oesophageal sphincter pressure. This finding is unlikely to be the result ofa denervation process involving opioid nerves. (Gut 1993; 34: 16-20) Idiopathic achalasia is a disease ofthe oesophagus characterised by absent peristalsis, impaired lower oesophageal sphincter relaxation after swallows and often a high lower oesophageal sphincter resting pressure.' Achalasia is thought to be determined by a visceral neuropathy which probably involves the vagal preganglionic and the postganglionic nerve fibres of the oesophagus.2 During the past years the attention has been focused mainly on the lower oesophageal sphincter, and some results suggest that noncholinergic inhibitory nerves are impaired4 whereas cholinergic innervation is at least partly preserved.Opioid nerves have been shown in the myenteric plexus of normal lower oesophageal sphincter in man" and various opioid receptors have been identified in the opossum lower oesophageal sphincter, in the sphincter muscle and the nerve fibres surrounding it.'" Furthermore, evidence exists that opioid peptides affect lower oesophageal sphincter motor function."-'5 In particular one study'4 showed that an opioid agonist, morphine, administered to healthy subjects determined a decrease and an opioid blocker, naloxone, an increase, although modest, in lower oesophageal sphincter pressure. The latter finding may suggest that endogenous opioids contribute to th...

Rapid air infusion into the oesophagus: Motor response in patients with achalasia and nonobstructive dysphagia assessed with high‐resolution manometry

“…impairment of inhibitory neural pathways due to degeneration of inhibitory ganglion cells in the myenteric plexus of the oesophagus and degenerative lesions in the vagal nerves and the dorsal motor nucleus). 5,[13][14][15][16] Studying oesophageal motility induced by rapid air infusion poses a few challenges in these patients before miotomy or pneumatic dilation is performed. On one hand, the oesophageal body is variably dilated before treatment, making it difficult to standardize distending stimuli; on the other, traditional quantitative variables of motility (i.e.…”

Effect of gluten‐free diet on preventing recurrence of gastroesophageal reflux disease–related symptoms in adult celiac patients with nonerosive reflux disease

“…Therefore, although the effects of gluten exorphins still remain to be fully elucidated, it could be argued that the gluten exorphins, opioid peptides identified in the enzymatic digests of gluten, could exert a morphine‐like activity on esophageal and gastric motility. However the motor effects of the morphine on gastroesophageal motility seem contradictory, as in fact while some authors described that morphine induces lower esophageal sphincter (LES) relaxation, decreases the resting LES pressure, 16 delays gastric emptying 17 —factors that could be involved in gastroesophageal reflux—others have suggested that morphine decreasing gastric fundal volume could decrease transient LES relaxation and gastroesophageal reflux 18 …”

Opioids in Gastroenterology: Treating Adverse Effects and Creating Therapeutic Benefits

“…Resting LES pressure is decreased both in health and in achalasia; swallow-induced LES relaxation is also significantly decreased by morphine in the healthy subjects. 39 A range of manometric abnormalities have been reported in patients with dysphagia using chronic opioids, such as impaired LES relaxation, high amplitude/velocity and simultaneous esophageal waves, 40 as well as esophagogastric junction outflow obstruction, higher integrated relaxation pressure, and lower distal latency on esophageal pressure topography. 41 Some of these findings are in contrast to the acute opioid effects cited previously.…”

“…Two studies have demonstrated an acute decrease in lower esophageal sphincter pressure by μ opioid receptor stimulation. 28,29 Nevertheless, the sum of these motor and secretory effects result in anorexia, nausea, emesis, impaired ability to evacuate the bowel, as well as abdominal spasm, cramps, and pain. 19,30 Decreased gastric, biliary, pancreatic and intestinal secretions interfere with digestion.…”